Key result
Intraperitoneal injection of 2-APB significantly inhibited hypoxia-induced increases in right ventricular systolic pressure by 38.6% in a mouse model of pulmonary hypertension.
Why the study?
Rodent models of experimental pulmonary hypertension are used to study disease mechanisms and test therapies, but standardized methods to phenotype pulmonary hemodynamics and vascular structure are needed.
Answers are grounded in this paper and cite their sources.
Pulmonary arterial hypertension is a progressive and fatal disease and rodents with experimental pulmonary hypertension (PH) are often used to study pathogenic mechanisms, identify therapeutic targets, and develop novel drugs for treatment. Here we describe a hands‐on set of experimental approaches including ex vivo lung angiography and histology and in vivo right heart catheterization (RHC) to phenotypically characterize pulmonary hemodynamics and lung vascular structure in normal mice and mice with experimental PH. We utilized Microfil polymer as contrast in our ex vivo lung angiogram to quantitatively examine pulmonary vascular remodeling in mice with experimental PH, and lung histology to estimate pulmonary artery wall thickness. The peripheral lung vascular images were selected to determine the total length of lung vascular branches, the number of branches and the number of junctions in a given area (mm−2). We found that the three parameters determined by angiogram were not significantly different among the apical, middle, and basal regions of the mouse lung from normal mice, and were not influenced by gender (no significant difference between female and male mice). We conducted RHC in mice to measure right ventricular systolic pressure, a surrogate measure for pulmonary artery systolic pressure and right ventricle (RV) contractility (RV ± dP/dtmax) to estimate RV function. RHC, a short time (4–6 min) procedure, did not alter the lung angiography measurements. In summary, utilizing ex vivo angiogram to determine peripheral vascular structure and density in the mouse lung and utilizing in vivo RHC to measure pulmonary hemodynamics are reliable readouts to phenotype normal mice and mice with experimental PH. Lung angiogram and RHC are also reliable approaches to examine pharmacological effects of new drugs on pulmonary vascular remodeling and hemodynamics.
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Xiong et al. (2021) studied Experimental pulmonary hypertension. 2-aminoethyl diphenylborinate (2-APB) vs. Vehicle (DMSO) was evaluated on Right ventricular systolic pressure (RVSP) (38.6% inhibition of hypoxia-induced increase, p=<0.001). Intraperitoneal injection of 2-APB significantly inhibited hypoxia-induced increases in right ventricular systolic pressure by 38.6% in a mouse model of pulmonary hypertension.
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